This Mentored Career Development Award will provide the essential support for a fellowship-trained surgical oncologist to conduct a translational research study evaluating nonsurgical options for preinvasive breast cancer. Patients will be accrued from a tertiary care multidisciplinary breast clinic housed within an NIH designated comprehensive cancer center as well as from an affiliated urban county hospital. Ductal carcinoma in situ (DCIS) will be diagnosed in over 50,000 women in the United States this year. Current breast surgery for DCIS does not differ from that undertaken for invasive breast cancer, despite the minimal metastatic potential for DCIS. A nonsurgical approach in patients with DCIS has previously not been possible as there has been no tool with which to follow DCIS. This prospective clinical trial will determine whether a course of preoperative hormonal therapy with an aromatase inhibitor (AI) in postmenopausal women results in a decrease in DCIS tumor volume as assessed by MRI. Secondary endpoints will consist of changes in immunohistochemical (IHC) and genomic markers of response. 40 postmenopausal patients diagnosed with DCIS on core biopsy without concurrent invasive cancer will be recruited for the study. Eligible women will undergo baseline mammography and MR] at study initiation and again following 3 months of treatment with an AI. Primary endpoints will be tumor volume and tumor diameter, as measured by MRI. Biomarkers consisting of IHC and genomic characteristics of the tumor will be assessed at baseline and at surgical excision to identify predictive and prognostic markers of response. While the current invasive treatments for DCIS are effective, they could represent overtreatment of at least half the women with DCIS who might never progress to invasive cancer. The long-term goal of this proposal is to effectively alter the treatment algorithm of DCIS so that nonsurgical interventions such as hormonal therapy could be instituted in the place of lumpectomy and radiation or mastectomy for at least a subset of patients. This project will provide a rare opportunity to directly evaluate both the clinical and biological response of DCIS to therapy without compromising patient safety or cancer treatment. Through patient participation in such studies, we can establish a foundation from which to plan novel, less aggressive treatment algorithms for patients with the earliest manifestations of breast cancer. We believe that a more tailored strategy for this group of patients is not only possible, but more appropriate than currently offered treatments. If patients could safely be spared from cancer progression while avoiding the morbidity of surgery and radiation for DCIS, the full benefit of early breast cancer detection could be realized.